Establishment of new prostate cancer metastatic model with androgen independent growth and identification of new mechanism of androgen-independency

新型雄激素非依赖性前列腺癌转移模型的建立及雄激素非依赖性新机制的鉴定

• 批准号: 22791487
• 负责人: NAIKI Taku
• 金额: $ 2.5万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791487/
• 关键词: 去勢抵抗性前立腺癌; 転移動物モデル; 分子標的治療; 前立腺癌; 動物モデル

We established androgen-independent prostate cancer cell line from TRAP tumor, and named PCai1, and previously reported the orthotopic metastatic models, and tail vein injection model using PCai1 cells. We investigate the GST-P expression of PCai1 by RT-PCR and Western blot. In addition, using GST-P-siRNA, we investigated the relationship between the cell growth and Reactive Oxygen Species(ROS) in PCai1.PCai1 cells had higher GST-P expression in mRNA and protein levels in Charcoal Stripped-FBS medium than in normal medium. GST-P knocked down by siRNA resulted in significant decrease of the proliferation rate in vitro. On the contrary, DCFH assay revealed that ROS was induced by GST-P-siRNA treat. Tumors metastasized in the bone marrow after intravenous injection expressed high levels of GST-P, while metastatic lesions in the lung and lymph nodes failed to express GST-P as seen in the case of the orthotopic implantation. GST-P might have the important roles in the prostate cancer growth and metastasis by the restriction of ROS.

我们从TRAP肿瘤中建立了雄激素非依赖性前列腺癌细胞系，命名为PCa 1，并报道了PCa 1细胞的原位转移模型和尾静脉注射模型。我们用RT-PCR和Western blot检测了PCa 1中GST-P的表达。此外，我们还利用GST-P-siRNA技术研究了PCa 1细胞生长与活性氧（ROS）的关系。PCa 1细胞在活性氧（ROS）浓度为100 μ mol/L的活性氧培养基中，GST-P的mRNA和蛋白表达水平均高于正常培养基。GST-P的siRNA敲低导致体外增殖率显著下降。DCFH检测显示GST-P-siRNA可诱导ROS的产生，骨髓转移瘤静脉注射后GST-P表达升高，而肺和淋巴结转移瘤原位种植后GST-P表达下降。GST-P可能通过抑制活性氧的产生而在前列腺癌的生长和转移中发挥重要作用。

项目成果

Glutathione oxidation-reduction system facilitates androgen independent prostate cancer growth

谷胱甘肽氧化还原系统促进不依赖雄激素的前列腺癌生长

• 发表时间: 2011
• 作者: Naiki T;Okamura T;Nagata D;Mori Y;Kawai N;Ogawa K;Akita H;Hashimoro Y;Tozawa K;Kohri K;Satoshi Anai;Naiki T
• 通讯作者: Naiki T

ラット前立腺癌モデル由来細胞株によるアンドロゲン非依存性前立腺癌転移モデルの確立

利用大鼠前列腺癌模型来源的细胞系建立雄激素非依赖性前列腺癌转移模型

• 发表时间: 2010
• 作者: 内木拓;朝元誠人;内木綾;戸澤啓一;白井智之;郡健二郎
• 通讯作者: 郡健二郎

再燃前立腺癌における酸化ストレス応答因子の役割

氧化应激反应因子在复发性前列腺癌中的作用

• 发表时间: 2011
• 作者: Naiki T;Okamura T;Nagata D;Mori Y;Kawai N;Ogawa K;Akita H;Hashimoro Y;Tozawa K;Kohri K;Satoshi Anai;Naiki T;内木拓
• 通讯作者: 内木拓